DESCRIPTION (provided by investigator): Migraine is a common chronic-episodic disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, often accompanied by neurological symptoms, and distinguished from tension-type headaches by the moderate to severe intensity, unilateral location, the presence of nausea, and sensitivity to activity and/or stimuli. The lifetime prevalence of migraine in women has been reported between 14-25 per cent with increasing prevalence during the childbearing years. Preeclampsia, a vascular disorder of pregnancy, characterized by hypertension and proteinuria, complicates up to 8 per cent of all pregnancies, and it is a leading cause of maternal morbidity worldwide. A handful of studies have documented an elevated risk of pregnancy-induced hypertension or preeclampsia among migraineurs. Methodological limitations hinder causal inference from available studies. We propose a prospective cohort study of 2,000 pregnant nulliparous women to further examine the relationship between migraines and preeclampsia. The overall aim of the proposed research is to evaluate whether, and to what extent, maternal pre-gestational history of migraines and migraines symptom during early pregnancy are associated with preeclampsia risk; and (2) to evaluate mechanistic hypotheses concerning the role of platelet aggregation and activation in preeclampsia. We will collect maternal blood samples during the first trimester of pregnancy. During in-person interviews, women will be asked to provide information regarding physician diagnosed migraine and migraine symptoms. Women who screen positive for migraine and/or who report a prior medical diagnosis of migraine will have a follow-up interview with a board certified neurologist to confirm migraine status. Labor and delivery medical records will be reviewed to collect information about the study pregnancy. Indices of maternal platelet aggregation and activation will be assessed using flow cytometric methods. Statistical analyses will focus on determining: (1) the extent to which a history of pre-gestational migraines is associated with subsequent risk of preeclampsia; (2) whether migraine symptoms in early pregnancy and medications used to treat migraines are independently associated with preeclampsia risk; and (3) whether biological markers of platelet aggregation and activation in early pregnancy, are associated with maternal migraine status and subsequent risk of preeclampsia. Increased knowledge concerning the epidemiology and pathophysiology of preeclampsia and migraines, particularly as they relate to pro- inflammatory platelet adhesion to leukocytes during pregnancy will aid in understanding underlying mechanisms and lead to the identification of possible prevention and therapeutic strategies. PUBLIC HEALTH RELEVANCE Migraine, a common chronic-episodic disorder characterized by severe debilitating headaches and autonomic nervous system dysfunction, has a lifetime prevalence of 14- 25 per cent in women. Preeclampsia, a vascular disorder of pregnancy, complicates up to 8 per cent of pregnancies, and is a leading cause of maternal morbidity worldwide. Some studies have documented an elevated risk of preeclampsia among women with migraines. Our proposed research will evaluate whether, and to what extent, maternal pre-gestational history of migraines and migraine symptoms during early pregnancy are associated with preeclampsia risk; and evaluate possible physiological mechanisms of this association concerning the role of platelet aggregation and activation in preeclampsia. Increased knowledge concerning the epidemiology and pathophysiology of preeclampsia and migraines, particularly as they relate to pro-inflammatory platelets adhesion to leukocytes during pregnancy will aid in understanding underlying mechanisms and lead to the identification of possible prevention and therapeutic strategies.